How do aseptic spray dryers differ from non-aseptic spray dryers?
Pharmaceutical production under aseptic conditions has to be a validated process that fulfills the requirements established
by the relevant authorities, including requirements for how to sterilise the plant and for maintaining of sterility throughout
the full production run. An aseptic spray dryer is differentiated from a non-aseptic one only in the requirements for sterilisation
and can be used for the same processes, such as particle engineering, lenient drying, scalability and use of organic solvents,
as a non-aseptic spray dryer.
The challenges of using spray drying in aseptic production mainly relate to three areas:
- plant sterilisation
- maintaining sterility during production
- product handling (e.g., filling of vials).
A fundamental difference between the use of a spray dryer compared with aseptic liquid and typically aseptic-lyophilised formulations
is that it requires aseptic powder filling into vials as opposed to aseptic liquid filling. In the case of lyophilisation,
vials must also be loaded prior to the drying process. However, aseptic powder filing is a well-established technology with
several providers in the market.
To ensure that sterility is maintained during spray drying, all gas entering and leaving the sterile drying zone must be adequately
filtered. The liquid formulation must also be adequately filtered. However, this may not always be possible, in which case
sterility must be ensured through other means, such as preparing the formulation under aseptic conditions using sterile components.
What methods are used for sterilising spray dryers?
An accepted method for the sterilisation of spray dryers that meets the requirements from drug approval authorities is the
key for wider use of spray drying in aseptic production. Traditionally, spray drying sterilisation methods have included:
- off-line sterilisation in a autoclave or sterilisation oven
- in-place sterilisation by dry heat
- in-place sterilisation by steam.
Off-line sterilisation is ideal for small plants that can be dismounted and assembled aseptically after sterilisation (e.g.,
inside an isolator). Small plants and the associated ductwork have a large surface area to volume ratio, which makes dry heat
sterilisation problematic, and off-line sterilisation offers a less complex solution compared with in-place sterilisation
In-place sterilisation by dry heat takes advantages of the fact that a spray dryer is designed for hot gas. However, the high
temperature requirements (typically 170 °C) and the limited heat capacity of air or nitrogen make it difficult to heat up
the inside surface of plant and ductwork where cold bridges are present.
Sterilisation by steam has been the preferred method for sterilisation in the pharmaceutical industry for decades and is used
extensively for lyophilisers. This method is also applicable for spray dryers if it is designed as a pressure vessel.
A novel sterilisation process for lyophilisers is H2O2, which is approved by both the FDA and the EMA. For spray dryers, H2O2 or other gases have not been used for sterilisation. Compared with the internal surfaces of a lyophiliser for vials, the
internal surfaces of a spray dryer are direct product contact surfaces. H2O2 or similar gases have not been used because they have not yet found general acceptance as means for sterilising direct product
Are there any difficulties associated with cleaninplace in preparing for aseptic spray drying
Clean-in-place (CIP) is a wellknown operation. As long as the CIP solutions do not impair the sterilisation of the spray dryer,
they are no different from other high-performance CIP systems used for non-aseptic pharmaceutical spray drying.
A filter integrity test is performed at the beginning and end of each cycle to ensure that the filters are functioning as
intended. Sterilisation is done by Steam-in-place (SIP) of the complete spray dryer, including feed line, nozzle and sterile
filters. SIP is performed as an evacuation and heating sequence followed by a steam sterilisation sequence at a minimum 121
°C for 20 min. The evacuation and heating sequence consists of a series of evacuations separated by steam injections, which
ensures the removal of air and heats the dryer prior to the sterilisation sequence itself. The removal of non-condensables
and the heating sequence is important for the plant to be fully sterilised. Crucial parameters include not only the sequence
of evacuation and steam injection, but also the duration of the steps and the pressure by which they are conducted.